Mouse Genome Informatics

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• at 12 months of age, no axon loss or degeneration in motor nerves
• mice start out with a 13% reduction of motor neurons
• further degeneration is delayed but ultimately reaches the same level of motor axon loss
• loss of axons in sensory neurons is increased
• slower development of ALS symptoms than in the presence of the transgene alone

Mouse Genome Informatics
Not Specified
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• at 6 months of age round Lewy body-like inclusions are visible in astrocytes
• number of inclusions increases with age
• inclusions have a dense core and a clear peripheral halo
• core consists of heterogeneous mass of short filamentous material covered with small granules
• periphery has a less dense and, in some cases, linear array of filaments
• abnormalities are evident in ventral motor neurons, small neurons of the central canal and interneurons of the dorsal horns, however, no abnormalities are observed in cortical or subcortical structures
• prior to onset of disease a small number of motor neurons exhibit a few diffuse aggregates that are immunoreactive for SOD1 and ubiquitin
• aggregates progress to rounded Lewy body-like or irregular inclusions in cell bodies
• end-stage transgenics exhibit large inclusions in a few neurons in cell bodies and axonal processes
• loss of motor neurons in ventral horn of spinal cord
• at 6.5 months a small number of large ventral motor neuron axons exhibit degeneration, although the loss is not significant
• at 8 months (disease onset) 25% of large motor axons are absent , of the remaining axons, 10% are undergoing degeneration and within another two weeks 66% are absent small caliber axons are not affected
• at 8 months 2.5% of large sensory axons are absent
• among large axons, 7.5% of dorsal root axons are absent at end stage

• weakened grip strength, the first indication of phenotype, is observed by 8 months and spreads rapidly to other limbs
• complete paralysis occurs two weeks after onset of weakened grip strength
• hindlimb paralysis is first observed at 8-10 months
• paralysis occurs 2-3 days after appearance of hindlimb weakness


Mouse Models of Human Disease
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:77600